355 research outputs found

    Multi-Objective Optimization of a Vehicle Body by Combining Gradient-based Methods and Vehicle Concept Modelling

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    Abstract In the automotive field, size optimization procedures can be combined with concept modelling approaches, in order to design a vehicle Body-In-White (BIW) model with optimal static and dynamic performances already in the early design stages. However, this specific optimization problem, with hundreds of design variables, limited design space and often conflicting objectives, makes the choice of the appropriate optimization method really difficult. The aim of this paper is to show an industrial case study, where two different implementations of the classical gradient-based (GB) method are used in combination with a technique for vehicle body concept modelling to achieve a multi-objective BIW optimization of a passenger car

    Wenn Muskeln die Nerven verlieren

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    In Deutschland werden jährlich ca. 300 Kinder mit einer oft fatalen neuro-nalen Krankheit, der Spinalen Muskelatrophie (SMA), geboren. Klinischfallen die Patienten mit einer schlaffen Lähmung der Extremitätenmusku-latur auf, in schweren Fällen lernen sie weder sitzen noch laufen. Lebens-bedrohlich wird die autosomal rezessive Erkrankung durch die begleiten-de Lähmung der Atemmuskulatur, die schwere Atemwegsinfektionen zurFolge hat. Daran versterben die Patienten häufig bereits im Kleinkindalter

    Peptide-Based Supramolecular Systems Chemistry

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    Peptide-based supramolecular systems chemistry seeks to mimic the ability of life forms to use conserved sets of building blocks and chemical reactions to achieve a bewildering array of functions. Building on the design principles for short peptide-based nanomaterials with properties, such as self-assembly, recognition, catalysis, and actuation, are increasingly available. Peptide-based supramolecular systems chemistry is starting to address the far greater challenge of systems-level design to access complex functions that emerge when multiple reactions and interactions are coordinated and integrated. We discuss key features relevant to systems-level design, including regulating supramolecular order and disorder, development of active and adaptive systems by considering kinetic and thermodynamic design aspects and combinatorial dynamic covalent and noncovalent interactions. Finally, we discuss how structural and dynamic design concepts, including preorganization and induced fit, are critical to the ability to develop adaptive materials with adaptive and tunable photonic, electronic, and catalytic properties. Finally, we highlight examples where multiple features are combined, resulting in chemical systems and materials that display adaptive properties that cannot be achieved without this level of integration

    Genotype–phenotype associations within the Li-Fraumeni spectrum: a report from the German Registry

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    Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by pathogenic TP53 variants. The condition represents one of the most relevant genetic causes of cancer in children and adults due to its frequency and high cancer risk. The term Li-Fraumeni spectrum reflects the evolving phenotypic variability of the condition. Within this spectrum, patients who meet specific LFS criteria are diagnosed with LFS, while patients who do not meet these criteria are diagnosed with attenuated LFS. To explore genotype-phenotype correlations we analyzed 141 individuals from 94 families with pathogenic TP53 variants registered in the German Cancer Predisposition Syndrome Registry. Twenty-one (22%) families had attenuated LFS and 73 (78%) families met the criteria of LFS. NULL variants occurred in 32 (44%) families with LFS and in two (9.5%) families with attenuated LFS (P value < 0.01). Kato partially functional variants were present in 10 out of 53 (19%) families without childhood cancer except adrenocortical carcinoma (ACC) versus 0 out of 41 families with childhood cancer other than ACC alone (P value < 0.01). Our study suggests genotype-phenotype correlations encouraging further analyses
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